Male HypogonadismEdit
Male hypogonadism is a clinical syndrome in which the body does not produce adequate androgens, most notably testosterone, or cannot use them effectively. The condition can arise from problems in the testes themselves (primary hypogonadism) or from disruptions in the signaling axis that controls testosterone production (secondary hypogonadism, involving the hypothalamus or pituitary). It appears in congenital forms during adolescence, but a sizable share of cases are related to aging or acquired illnesses that gradually erode androgen output. In everyday practice, clinicians distinguish these causes because they influence treatment choices, including whether fertility is a goal and how aggressively to monitor risks.
The impact of low androgens on men is far from trivial. Common symptoms include diminished libido and sexual function, fatigue, a decline in lean body mass and strength, increased adiposity, mood disturbances, and reduced bone mineral density, which raises the risk of osteoporosis and fractures. These effects can diminish quality of life, work productivity, and overall health. Diagnosis and management are therefore oriented toward relieving symptoms, improving metabolic health when possible, and guiding patients through the trade-offs of available therapies. The condition is relevant to a broad array of medical specialties, and the approach to care often blends primary prevention, targeted pharmacotherapy, and attention to comorbidities bone density cardiovascular disease.
Pathophysiology and classification
Male hypogonadism can be categorized by where the problem originates:
Primary hypogonadism (testicular failure): The testes fail to produce adequate testosterone despite normal or elevated signaling from the brain. Common causes include genetic conditions such as Klinefelter syndrome, testicular injury or infection, prior chemotherapy or radiation, and undescended testes. In this form, levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are typically elevated as the pituitary attempts to stimulate the underperforming testes.
Secondary hypogonadism (hypothalamic-pituitary dysfunction): The brain’s signaling is inadequate or inappropriate. Causes include obesity and metabolic syndrome, pituitary tumors or injury, inflammatory or systemic illnesses, opioid use, hyperprolactinemia, and certain genetic or systemic disorders. In secondary hypogonadism, LH and FSH are usually low or inappropriately normal.
Late-onset hypogonadism (often termed age-related hypogonadism): Testosterone levels decline gradually with age in many men, often in the setting of coexisting chronic illnesses such as obesity or metabolic syndrome. Whether this constitutes a distinct disease or a part of aging remains a subject of professional debate and varies by guideline.
Testosterone production follows a diurnal pattern in younger men, being highest in the morning. Because measurements can vary with time of day and assay methods, clinicians typically confirm low values with repeat testing on separate mornings before making a diagnosis. In primary versus secondary forms, hormone profiles commonly differ, with LH and FSH helping to distinguish the root cause.
Diagnosis and assessment
Diagnosis rests on symptom concordance with biochemical evidence of androgen deficiency. A practical approach includes:
Symptoms and signs: Diminished libido, erectile difficulties, fatigue, loss of muscle mass, increased abdominal fat, mood or cognitive changes, hot flashes, breast tissue changes, or signs of osteoporosis.
Biochemical testing: Total serum testosterone is the starting point, preferably measured in the morning on at least two occasions. If total testosterone is low or borderline, a free or bioavailable testosterone measure can be informative, especially when sex hormone–binding globulin (SHBG) is altered. Concurrent testing typically includes LH and FSH to categorize the disturbance, prolactin to screen for pituitary causes, and sometimes estradiol or other pituitary hormones to refine the evaluation.
Screen for contributory conditions: Sleep apnea, obesity, metabolic syndrome, diabetes, and cardiovascular risk factors warrant attention, as they can both contribute to hypogonadism and be affected by its treatment. Bone density testing (bone density or osteoporosis) is commonly considered given the association with reduced bone strength.
Fertility considerations: Because testosterone replacement can suppress spermatogenesis, clinicians discuss fertility goals with patients before initiating certain therapies. When fertility is a priority, alternative strategies may be pursued, such as agents that stimulate testicular production or gonadotropin therapy.
Imaging and secondary evaluation: If a pituitary or hypothalamic lesion is suspected, pituitary MRI or related endocrine testing may be appropriate. In congenital cases, genetic counseling and testing may be relevant.
Treatment options and management
The overarching aim of therapy is to relieve symptoms, improve functional status and metabolic health where possible, and minimize risks. Treatment is tailored to the individual, with particular attention to fertility desires, comorbidities, and the patient’s values.
Testosterone replacement therapy (TRT): TRT is the most widely used treatment for men with confirmed androgen deficiency who are not seeking fertility. Available forms include transdermal gels or patches, intramuscular or subcutaneous injections, and subcutaneous or implanted pellets. Treatment is typically continued long term, with regular monitoring.
- Goals and monitoring: After starting TRT, clinicians check serum testosterone to ensure therapeutic levels, and monitor hematocrit or hemoglobin (to watch for erythrocytosis), lipid profile, liver enzymes where relevant, and metabolic parameters. Prostate health monitoring, including digital rectal exam and prostate-specific antigen (PSA) testing, is commonly advised for men at standard risk, consistent with broader prostate cancer screening guidelines.
- Benefits and risks: TRT can improve energy, mood, sexual function, bone density, and some metabolic parameters. Potential risks include erythrocytosis, sleep apnea, acne or skin irritation, edema, and possible effects on prostate growth. The balance of benefits and risks varies by age, baseline health, and the presence of comorbid conditions.
- Fertility considerations: TRT may suppress endogenous testosterone production and impair spermatogenesis, potentially reducing fertility. For men who wish to preserve or restore fertility, alternative approaches such as gonadotropin therapy or selective estrogen receptor modulators may be considered, under specialist guidance.
Non-testosterone therapies: When fertility is a priority or when TRT is contraindicated, other strategies may be used to elevate androgen activity or stimulate production. These include pulsatile gonadotropin-releasing hormone (GnRH) therapy, human chorionic gonadotropin (hCG) to stimulate testosterone production in the testes, and, in some cases, gonadotropins (LH and FSH) to support spermatogenesis. Clomiphene citrate and selective estrogen receptor modulators can be considered in certain men with secondary hypogonadism to raise endogenous testosterone without suppressing fertility.
Lifestyle interventions: Weight loss, physical activity, and management of comorbid conditions such as diabetes or sleep apnea can improve natural testosterone levels and overall well-being. Diet and exercise programs are often recommended in conjunction with pharmacologic or fertility-focused therapies.
Fertility and family planning: For men who want to father children, preserving or restoring fertility is a central concern. Clinicians may prioritize treatments that maintain or enhance spermatogenesis, or they may pursue assisted reproductive techniques if needed.
Special populations and cautions: In men with a history of prostate cancer or active prostate issues, TRT decisions are made cautiously in collaboration with oncology and urology specialists, balancing cancer risk with symptom burden and quality of life. The broader literature does not demonstrate a clear, universal cancer risk from TRT, but individual risk assessment remains essential.
Controversies and debates
The field continues to grapple with several unsettled questions, and the conservative emphasis on evidence-based practice underlines the importance of individualized care:
Definitions and measurement: Testosterone assays vary in accuracy, and single measurements can misclassify a man’s status. A conservative practice often requires confirmatory testing and consideration of free or bioavailable testosterone if SHBG is abnormal. The threshold used to define deficiency (for example, total testosterone around 300 ng/dL or 10.4 nmol/L) is debated, with some arguing for a symptom-driven approach rather than a hard numeric cutoff.
Late-onset hypogonadism as a distinct entity: Whether aging-related declines in testosterone constitute a discrete syndrome with a clear treatment rationale is contested. Proponents emphasize symptom improvement and quality-of-life benefits in selected patients, while critics caution against medicalizing normal aging without robust evidence of net benefit.
Cardiovascular safety: Studies on the cardiovascular effects of TRT have yielded mixed results. Some analyses suggest neutral or even favorable effects on metabolic parameters, while others indicate potential increased risk for adverse cardiovascular events or thrombosis in certain populations. Clinicians weigh these uncertain data, especially in men with existing cardiovascular disease or risk factors, and emphasize informed consent and shared decision-making.
Prostate health and cancer risk: The long-standing concern that testosterone could promote prostate cancer remains a topic of discussion. Large guidelines generally do not endorse TRT as a clear cause of prostate cancer, but they advocate careful screening and individualized risk assessment, particularly in men with a prior history of prostate disease. This area remains open to further research.
Medicalization and access: Some critics worry about overdiagnosis and overtreatment driven by pharmaceutical marketing or patient demand, while others stress that quality of life, functional health, and independence in older men deserve legitimate consideration. From a policy standpoint, insurance coverage, cost, and access to properly supervised therapy are ongoing debates, especially for aging populations with multiple comorbidities.
Fertility versus treatment goals: When fertility is desired, TRT is often not the optimal long-term solution. The balance between relieving symptoms and preserving reproductive potential leads to individualized plans that may favor non-androgenic strategies or fertility-preserving regimens rather than standard testosterone therapy.